A referral-based program for cognitive and genetic AD risk assessment in a primary care setting is feasible, acceptable to patients, and yielded a more demographically diverse sample than an AD prevention registry.Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by cognitive alterations, visual hallucinations, and motor impairment. Diagnosis is based on type and timing of clinical manifestations; however, determination of clinical subtypes is challenging. The utility of blood DNA methylation as a biomarker for Lewy body disorders (LBD) is mostly unexplored.
We performed a cross-sectional analysis of blood methylation in 42 DLB and 50 PDD cases applying linear models to compare groups and logistic least absolute shrinkage and selection operator regression to explore the discriminant power of methylation signals.
DLB blood shows differential methylation compared to PDD. Some methylation changes associate with core features of LBD. Sets of probes show high predictive value to discriminate between variants.
Our study is the first to explore LBD blood methylation. Despite overlapping clinical presentation, we detected differential epigenetic signatures that, if confirmed in independent cohorts, could be developed into useful biomarkers.
Our study is the first to explore LBD blood methylation. Despite overlapping clinical presentation, we detected differential epigenetic signatures that, if confirmed in independent cohorts, could be developed into useful biomarkers.Early-onset Alzheimer's disease (EOAD) is generally known as a dominant disease due to highly penetrant pathogenic mutations in the amyloid precursor protein, presenilin 1 and 2. However, they explain only a fraction of EOAD patients (5% to 10%). Furthermore, only 10% to 15% of EOAD families present with clear autosomal dominant inheritance. Studies showed that only 35% to 60% of EOAD patients have at least one affected first-degree relative. Parent-offspring concordance in EOAD was estimated to be less then 10%, indicating that full penetrant dominant alleles are not the sole players in EOAD. We aim to summarize current knowledge of rare variants underlying familial and seemingly sporadic Alzheimer's disease (AD) patients. Genetic findings indicate that in addition to the amyloid beta pathway, other pathways are of importance in AD pathophysiology. We discuss the difficulties in interpreting the influence of rare variants on disease onset and we underline the value of carefully selected ethnicity-matched cohorts in AD genetic research.Recent research has found that World Trade Center (WTC) responders in their mid-50s have an elevated prevalence of mild cognitive impairment (MCI) that is associated with neural degeneration and subcortical thinning. This article extends our understanding of the molecular complexity of MCI through gene expression profiling of blood.
The transcriptomics of 40 male WTC responders were profiled across two cohorts (discovery nine MCI and nine controls; replication 11 MCI and 11 controls) using CITE-Seq at single-cell resolution in blood.
Comparing the transcriptomic signatures across seven major cell subpopulations, the largest differences were observed in monocytes in which 226 genes were differentially expressed. Pathway analysis on the genes unique to monocytes identified processes associated with cerebral immune response.
Our findings suggested monocytes may constitute a key cell type to target in blood-based biomarker studies for early detection of risk of MCI and development of new interventions.
Our findings suggested monocytes may constitute a key cell type to target in blood-based biomarker studies for early detection of risk of MCI and development of new interventions.Background Early identification of cognitive decline is critical for identifying individuals for inclusion in clinical trials and for eventual care planning. Methods A sample (ages 60-90 years) of consensus-diagnosed, community-dwelling Blacks (61 cognitively typical [HC], 28 amnestic mild cognitive impairment [aMCI], and 14 nonamnestic MCI [naMCI]) were recruited from the Michigan Alzheimer's Disease Research Center and the Wayne State University Institute of Gerontology. Participants received two resting state electroencephalograms (rsEEG, eyes closed) between which they engaged in a visual motion direction discrimination task. rsEEG %change current source densities across all frequency bands and regions of interest were calculated. Results EEG current density was not different across groups for pre-task resting state. However, compared to HC, aMCI showed significantly greater declines at temporal and central cortical sites, while naMCI showed significant parietal declines. Conclusion This novel approach of post-pre/cognitive challenge rsEEG successfully discriminated older persons with MCI from those without was sensitive to cognitive decline.Neuropsychiatric symptoms (NPS) in dementia are associated with poor cognitive outcomes in longitudinal studies. Whether this is due to differences in symptom burden between persons (BP) or changes within persons (WP) is unknown.
Patients with mild Alzheimer's disease (AD, n = 111) and Lewy-body dementia (LBD, n = 85) were assessed annually for 8 years. We modelled the association between NPS assessed by the Neuropsychiatric Inventory (NPI) and Mini-Mental State Examinations (MMSE) using Tobit mixed-effects model with NPS as individual means over time (BP) and its deviance (WP).
The association between higher NPS and poorer cognitive outcomes was mostly due to BP differences for the NPI-total score, and in particular for delusions, hallucinations, agitation, aberrant motor behavior, and apathy scores.
The NPS trait (BP) effect on cognitive decline is considerably stronger than the state effect (WP). https://www.selleckchem.com/GSK-3.html Clinically, long-term rather than episodic NPS better identifies patients with poor cognitive outcomes.
The NPS trait (BP) effect on cognitive decline is considerably stronger than the state effect (WP). Clinically, long-term rather than episodic NPS better identifies patients with poor cognitive outcomes.